Beyond anti inflammatory drugs for rheumatoid arthritis... the arthritis methotrexate story
by Nathan Wei, MD, FACP, FACR
Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.
Click here: Second Opinion Arthritis Treatment Kit
For arthritis, methotrexate is the “workhorse” disease modifying drug.
It is used as a first line disease modifying drug by most rheumatologists because it is effective, the onset of action is relatively fast, it is easy to use, and the effect seems to be long-lasting. At lower doses it has anti-inflammatory effects. At higher doses, it is an anti-metabolite blocking DNA synthesis and slowing proliferation of cells.
Indications for methotrexate use include rheumatoid arthritis, psoriatic arthritis, juvenile rheumatoid arthritis, reactive arthritis, systemic lupus erythematosus, myositis, and other types of inflammatory arthritis.
Methotrexate is rapidly absorbed after oral intake. The method used by most rheumatologists is to have the patient take their dose of methotrexate once a week. The medicine is taken orally.
Sometimes, in patients with severe arthritis, methotrexate is administered intravenously, the first few doses (first six weeks) to “prime the pump.”
The usual starting dose is 7.5 to 10 mgs orally once a week. The dose is increase by 2.5 mgs every 4 weeks until the desired effect is achieved. Maximum doses top out at 20-25 mgs per week. I rarely use a dose higher than 17.5 mgs.
Monitoring includes measurements of complete blood count, liver function, and kidney function every two weeks while the dose is being adjusted upward and then every four weeks when the patient has reached their maintenance dosage.
The drug is strongly bound by proteins in the blood. It is eliminated by excretion through both the kidneys as well as liver. Methotrexate generally works within 4-8 weeks with peak effectiveness at four to six months.
Nausea and fatigue may develop in the first 24 hours after dosing. Supplemental folic acid is recommended. Folic acid is also useful in minimizing the occurrence of mouth sores, another possible side-effect.
Liver function abnormalities may develop in up to 60 per cent of patients. However, these abnormalities respond to dose reduction, as a rule. Long term liver problems do not appear to be as much of a concern as once thought. However, patients with underlying liver problems, e.g. alcohol related problems, hepatitis, cirrhosis, etc. should not take this drug.
Other contraindications include hypersensitivity to the drug, pregnancy (it is terribly teratogenic), low white cell counts, and HIV infection.
Special precautions are needed for both men and women who are considering conception. Contraception is advised before starting methotrexate. This should be continued for one to three months after stopping methotrexate.
Lung hypersensitivity may develop and patients on methotrexate can develop life-threatening pneumonia.
Other troublesome side effects include, hair loss, sensitization of the skin to sunlight, and elevated blood uric acid levels.
Methotrexate toxicity is increased in the presence of abnormal kidney function.
Drug interactions to be mindful of include additive toxicities when used in combination with other immunosuppressive drugs, an increase in bone marrow toxicity when sulfa drugs are used, minor increases in methotrexate blood level with concurrent use of non-steroidal anti-inflammatory drugs, and increased toxicity when used with probenecid.
When used in treating rheumatoid arthritis, methotrexate may increase the frequency and size of rheumatoid nodules.
Methotrexate seems to have additive or even synergistic effects on arthritis when used in combination with sulfasalazine, and hydroxychloroquine.
For rheumatoid arthritis, itworks best when combined with a biologic.
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